Role of insulin-like growth factor binding proteins in 1alpha,25-dihydroxyvitamin D(3)-induced growth inhibition of human prostate cancer cells

BACKGROUND: The mechanisms underlying 1alpha,25-dihydroxyvitamin D(3) (1,25D)-induced growth inhibition of human prostate cancer cells have not been fully elucidated. To determine whether alterations in the insulin-like growth factor (IGF) signaling axis are associated with 1,25D-induced growth inhibition, we examined the ability of 1,25D to regulate expression of IGF binding proteins (IGFBPs) in human prostate cancer cell lines. METHODS: Northern and Western blot analyses were used to detect 1,25D-induced alterations in IGFBP expression. Additional in vitro studies were performed to determine the role of IGFBP-3 in 1,25D-induced growth inhibition. RESULTS: 1,25D decreased mRNA levels of the growth stimulatory IGFBP-2 and induced IGFBP-3 mRNA in LNCaP and C4-2 cells. 1,25D treatment also increased secreted IGFBP-3 protein levels in prostate cancer cell lines sensitive to 1,25D growth inhibition but had little effect on IGFBP-3 expression in 1,25D-resistant DU145 cells. However, recombinant IGFBP-3 had only a minor effect on LNCaP cell growth in the presence of serum. Furthermore, siRNA duplexes that reduced IGFBP-3 expression did not alter 1,25D growth inhibition in either LNCaP or PC-3 cell lines grown in serum-containing media. CONCLUSIONS: Our studies indicate 1,25D-induced up-regulation of IGFBP-3 is not required for the growth inhibitory effects of 1,25D in prostate cancer cells grown in serum-containing media.     

A cognitive typology of alcoholism: implications for treatment outcome

The present study related patterns of alcohol-related cognitive deficits to the adjustment of the alcoholic at 2-year posttreatment follow-up. Patterns of cognitive control, based on the extent to which the individual utilized information concerning contemplated action (i.e., internal scanning), were studied within a sample of 42 male alcoholics shortly after the beginning of treatment. Adjustment scores at 2-year follow-up were determined by the subject's level of functioning in a variety of life-functioning domains (based on phone interviews with subjects and collateral sources). More effective internal scanning proved to be predictive of better adjustment 2 years following the assessment. In addition, alcoholics less aware of internal cues, defined as narrow internal scanners, more often reported drinking to reduce tension than did broad scanning alcoholics. The narrow internal scanning alcoholics also were slower learners at an electromyographic biofeedback training task than were the broad internal scanning alcoholics. These findings are interpreted in the context of a cognitive typology of alcoholism based on relative skills/deficits in internal cue processing. Factors relating to differential responsivity to treatment are discussed, and concomitant implications for treatment are noted.     

Poor outcome of two children with relapsed state stage IV alveolar rhabdomyosarcoma after allogeneic stem cell transplantation

The authors report on 2 boys, 11(1/2) and 13 years old, who received allogeneic stem cell transplantation (alloSCT) from their HLA-identical sibling after relapse of stage IV alveolar rhabdomyosarcoma. Both patients were transplanted in a non-remission status. After alloSCT both patients experienced disease progression at the primary tumor location sites and died due to the underlying disease 146 and 379 days after transplantation. The authors conclude that an alloSCT derived graft versus tumor effect might not be effective enough to overcome alveolar rhabdomyosarcoma when transplantation is carried out in a nonremission status.